Toll receptors, which were first discovered in Drosophila, are type I transmembrane protein having leucine-rich repeats (LRRs) in the extracellular portion of the protein, and one or two cysteine-rich domains. The mammalian homologs of the Drosophila Toll receptors are known as “Toll-like receptors” (TLRs). TLRs have been have been shown to play a role in innate immunity by recognizing microbial particles and activating immune cells against the source of these microbial particles.
Currently, ten types of Toll-like receptors have been identified, TLRs 1-10. These TLRs are characterized by the homology of their intracellular domains to that of the IL-1 receptor, and by the presence of extracellular leucine-rich repeats.
TLRs are activated by different types of microbial particles known as pathogen-associated molecular patterns (PAMPs). For example, TLR4 is primarily activated by lipopolysaccharide (LPS), while TLR2 is activated by lipoteichoic acid (LTA), lipoarabinomannan (LAM), lipoprotein (BLP), and peptideglycans (PGN). It is therefore possible that any given microbe can stimulate several different TLRs in parallel at any given time during an infection.
In addition, certain TLRs have been shown to require the presence of accessory proteins in order to function. For example, TLR4 forms a complex with myeloid differentiation protein-2 (MD-2) on the cell surface. The MD-2 protein has been found to interact directly with TLR4, and MD-2 has the ability to enable post-translational modifications of TLR4, as well as facilitate its transport to the cell surface. CD14 is another protein that has been linked to TLR4 function, and in addition, CD14 has also been implicated in TLR2 recognition of microbes.